Abstract: Astrocytes are the most abundant cell type in the human brain, yet we still do not fully understand the impact of astrocytes on human disease. In this proposal we will begin to uncover the role of astrocytes in regulating cortical plasticity using several new technologies including quantitative mass spectroscopy and microfluidic chambers developed to rapidly identify astrocyte factors that are released in response to the paracrine signals acetylcholine (ACh) or norepinephrine (NE) and that are likely to impact plasticity in both the developing and adult brain. Additionally, we will take advantage of the outstanding stem cell and proteomic centers here at UCSF to ask whether astrocytes derived from somatic cells from individuals on the autism spectrum secrete altered levels of synaptogenic factors. Using a combined microfluidic chamber and imaging system we will screen for effects on synapse formation and function using astrocytes derived from autism patients and familial controls. These studies have the potential to uncover the role of glial cells both in regulating normal plasticity and in disease states. Public Health Relevance: These studies will investigate the role of astrocytes in autism spectrum disorders and in cortical plasticity. Astrocytes can profoundly regulate synapse formation and function and both of these are disrupted in autism spectrum disorders.